The goal of this project is the identification of heritable characteristics of ion transport which may distinguish individuals with a primary affective disorder from normal controls. A study of sodium potassium stimulated adenosine triphosphatase (Na ion-K ion-ATPase), a cation transport enzyme, is in progress. The level of this membrane enzyme is lowered in depressed patients but returns to normal during remission. A twin study will serve to determine heritability of this enzyme. We are also looking at effects of amphetamine and arecoline on this enzyme. New results from other centers have led us to reopen our interest in lithium transport. We are now engaged in a collaborative program of research on the lithium erythrocyte/plasma ratio in euthymic patients. We have confirmed that Bipolar patients have higher ratios than controls. We propose to investigated this ratio in relatives of patients to test whether it may be a genetic vulnerability factor in affective disorder.